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Differential effect of quinpirole and 7‐OH‐DPAT on the spontaneous [ 3 H]‐dopamine efflux from rat striatal synaptosomes
Author(s) -
GarcíaSanz Alicia,
Badia Albert,
Clos M. Victoria
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(200104)40:1<65::aid-syn1027>3.0.co;2-i
Subject(s) - quinpirole , chemistry , agonist , autoreceptor , endocrinology , efflux , medicine , dopamine , microdialysis , extracellular , pharmacology , receptor , biology , biochemistry
The effect of quinpirole and 7‐OH‐DAPT, two D 2 ‐like agonists, were examined using superfused rat striatal synaptosomes to study the autoregulation of spontaneous [ 3 H]‐dopamine ([ 3 H]‐DA) release. Basal [ 3 H]‐DA efflux was Ca 2+ ‐dependent by ∼45% and was inhibited by cadmium 10 μM by 24%. Quinpirole (1 nM to 3 μM) inhibited spontaneous [ 3 H]‐DA efflux in a concentration‐dependent manner (pEC 50 = 7.56 ± 0.07 and E max = 26 ± 0.09%) and this effect was competitively antagonized by haloperidol (0.3–1 nM) (apparent pA 2 = 9.61 ± 0.08). In addition, activation of the D 2 DA autoreceptor by quinpirole only modulates the calcium‐dependent component of [ 3 H]‐DA efflux. Low concentrations of a putative‐selective D 3 DA agonist, (±)‐7‐OH‐DPAT (0.03–0.1 μM), inhibited spontaneous [ 3 H]‐DA release by 13% ( P < 0.05), but higher drug concentrations (≥1 μM) increased basal [ 3 H]‐DA efflux in a concentration‐dependent, nonsaturable, but reversible manner. Haloperidol (1–10 nM) reversed the (±)‐7‐OH‐DPAT‐induced inhibition, but not the increase in [ 3 H]‐DA outflow. The effect of (±)‐7‐OH‐DPAT was mimicked by (+)‐7‐OH‐DPAT. However, another putative D 3 DA agonist, PD 128,907 (1 nM to 3 μM), decreased spontaneous tritium efflux (maximal inhibition of 19 ± 3.06% at 3 μM, P < 0.01). The effect of 7‐OH‐DPAT 10 μM was independent of the presence of extracellular Ca 2+ , since its effect on basal [ 3 H]‐DA outflow was not significantly modified in a 200 nM free‐Ca 2+ medium. In addition, the 7‐OH‐DPAT‐induced enhancement of basal [ 3 H]‐DA efflux does not involve depolarization of nerve terminals or the reversal of the DA uptake system, as tetrodotoxin (1 μM) and nomifensine (1μM) did not modify the effect of 7‐OH‐DPAT 10 μM. The present data indicate that activation of D 2 DA autoreceptor subtype by quinpirole inhibits Ca 2+ ‐dependent spontaneous [ 3 H]‐DA efflux. 7‐OH‐DPAT activates the D 2 DA autoreceptor at low concentrations, whereas its action in releasing [ 3 H]‐DA effect is not receptor‐mediated and could involve other mechanisms other than either conventional vesicular exocytosis or the DA uptake system. Synapse 40:65–73, 2001. © 2001 Wiley‐Liss, Inc.